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The psychedelic research renaissance is gaining traction. Preliminary clinical studies of the hallucinogenic fungi, psilocybin, with psychological support, have indicated improvements in mood, anxiety and quality of life. A seminal, open-label study demonstrated marked reductions in depression symptoms in participants with treatment-resistant depression (TRD). The associated neurobiological processes involve alterations in brain connectivity, together with altered amygdala and default mode network activity. At the cellular level, psychedelics promote synaptogenesis and neural plasticity. Prompted by the promising preliminary studies, a randomized, double-blind trial has recently been launched across Europe and North America to investigate the efficacy of psilocybin in TRD. One of these centres is based in Ireland – CHO Area 7 and Tallaght University Hospital. The outcome of this trial will determine whether psilocybin with psychological support will successfully translate into the psychiatric clinic for the benefit of patients.
The maintenance of biodiversity in tropical forests is thought to be dependent on fine-scale mechanisms of niche partitioning that allow species to coexist. This study examined whether three species of short-tailed fruit bat that co-occur at a lowland tropical forest site in Costa Rica (Carollia castanea, C. perspicillata, C. sowelli) avoid inter- and intraspecific competition through dietary specialization on species in the genus Piper. First, dietary composition was examined using faecal samples (N = 210), which yielded three main findings: (1) bat species and sexes vary in overall reliance on fruits of Piper, with a higher percentage of seeds of Piper detected in the diets of C. castanea (98.2%) and females (91.5%); (2) adults and juveniles partition species of Piper by habitat, with a lower percentage of mid- to late-successional species of Piper detected in adults (20.8%); and (3) overall, there is a strong dietary overlap among and within the three species of Carollia. Second, controlled choice experiments were conducted with individual bats (N = 123) to examine preferences for different species of Piper. These results indicated few differences in Piper preference based on bat species, sex, age class or reproductive status, suggesting preference is not the primary mechanism shaping the observed differences in dietary composition. Overall, the dietary composition and preference similarities suggest there is strong competition both among and within the three species of Carollia for food resources.
We report here for the first time the presence of Ophelimus mediterraneus sp. n. in Mediterranean Europe. This species appears to be closely related to Ophelimus maskelli, a well-known invasive pest of Eucalyptus. Based on molecular (cytochrome oxidase I, 28S), morphological (multivariate ratio analysis) and bio-ecological investigations, our study gives unambiguous relevant criteria that allow the discrimination between these two species. A full description of O. mediterraneus sp. n. is also provided. The geographic distribution of O. mediterraneus sp. n. as well as its impact on Eucalyptus species needs to be more widely assessed since its presence may have been confused with O. maskelli in their sympatric introduced areas. Further investigations of potential parasitoids in the native area may thus be welcomed to evaluate classical biological control achievability.
Patients treated with antipsychotics, regardless of psychiatric diagnosis, are at risk for developing tardive dyskinesia (TD), a potentially debilitating drug-induced movement disorder. Valbenazine (INGREZZA; VBZ) is a novel vesicular monoamine transporter 2 (VMAT2) inhibitor approved to treat TD in adults. Data from KINECT 4 (NCT02405091) were analyzed to evaluate the long-term effects of VBZ in adults with schizophrenia/schizoaffective disorder (SZD) or mood disorder (MD) and moderate or severe TD.
KINECT 4 included open-label treatment (48weeks) followed by washout (4weeks). Entry requirements included: moderate or severe TD, qualitatively assessed at screening by a blinded, external reviewer; DSM diagnosis of SZD or MD; psychiatric stability (Brief Psychiatric Rating Scale score <50). Stable concomitant psychiatric medications were allowed. Dosing was initiated at 40mg, with escalation to 80mg at Wk4 if participants had a Clinical Global Impression of Change-TD score of ≥3 (minimally improved to very much worse) and tolerated 40mg. A reduction to 40mg was allowed if 80mg was not tolerated (80/40mg); participants unable to tolerate 40mg were discontinued. Safety was the primary focus, but the Abnormal Involuntary Movement Scale (AIMS) total score (sum of items 1–7) was used to evaluate changes in TD. Mean changes from baseline (BL) in AIMS total score (rated by on-site investigators) were analyzed descriptively. Safety assessments included treatment-emergent adverse events (TEAEs) and psychiatric scales (Positive and Negative Syndrome Scale [PANSS], Calgary Depression Scale for Schizophrenia [CDSS], Montgomery-Åsberg Depression Rating Scale [MADRS], Young Mania Rating Scale [YMRS], and Columbia-Suicide Severity Rating Scale [C SSRS]).
Of 163 participants in the analyses, 103 completed the study. Adverse events (n=26) was the most common reason for discontinuation. Analyses included 119 participants with SZD (40mg=37; 80mg=76; 80/40mg=6) and 44 with MD (40mg=8; 80mg=31; 80/40mg=5). At Wk48, mean improvements from BL in AIMS total score were: SZD (40mg, –10.1; 80mg,–10.7); MD (40mg, 10.2; 80mg: –11.6). AIMS total scores at Wk52 (end of washout) indicated a return toward BL levels. Compared to SZD, the MD subgroup had a higher incidence of any TEAE (84% vs 61% [all doses]) but fewer TEAEs leading to discontinuation (7% vs 18%). Urinary tract infection was the most common TEAE in the MD subgroup (18%); somnolence and headache were most common in the SZD subgroup (7% each). Psychiatric status remained stable from BL to Wk48: SZD (PANSS positive, –0.7, PANSS negative, –0.6; CDSS, –0.7); MD (MADRS, –0.3; YMRS, –0.3). Most participants (95%) had no change in C-SSRS score during the study.
Sustained and clinically meaningful TD improvements were observed with VBZ, regardless of primary psychiatric diagnosis. VBZ was generally well tolerated and no notable changes in psychiatric status were observed.
Funding Acknowledgements: Supported by Neurocrine Biosciences, Inc.
To evaluate the long-term safety and tolerability of once-dailyvalbenazine in adults with tardive dyskinesia(TD).
Data were pooled from KINECT 3 (NCT02274558: 6-week double-blind placebo-controlled period, followed by a 42-week double-blind extension and 4-week drug-free washout) and KINECT 4 (NCT02405091: 48-week open-label treatment period and 4-week drug-free washout). KINECT 3/4 study completers could enroll in a subsequent rollover study (NCT02736955: up to 72weeks of open-label treatment or until valbenazine became commercial available); data from this study were described separately for this analysis. Valbenazine dose groups (40 and 80mg) were pooled for analysis. Safety assessments included treatment-emergent adverse events (TEAEs) and the Columbia-Suicide Severity Rating Scale (C-SSRS). Psychiatric status was assessed in KINECT 3 and KINECT 4 using the following measures: Positive and Negative Syndrome Scale (PANSS) total score and Calgary Depression Scale for Schizophrenia (CDSS) in participants with schizophrenia/schizoaffective disorder; Montgomery-Åsberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS) in participants with a mood disorder.
Analyses included 304 KINECT 3/4 participants and 160 rollover participants. In KINECT 3/4, the summary of TEAEs was as follows: any TEAE (71.7%), serious TEAE (16.8%), and discontinuation due to TEAE (15.5%). TEAEs reported in ≥5% of all KINECT 3/4 participants were headache (8.9%), urinary tract infection (8.9%), somnolence (7.9%), fatigue (6.3%), dizziness (5.9%), and suicidal ideation (5.6%). The summary of TEAEs from the rollover study was as follows: any TEAE (53.1%), serious TEAE (10.0%), and discontinuation due to TEAE (5.6%). The most common TEAEs in the rollover study were back pain and urinary tract infection (4.4%, each); no TEAE was reported in ≥5% of participants. Minimal changes in psychiatric status were observed in KINECT 3/4, as indicated by mean score changes from baseline to Week 48 in participants with schizophrenia/schizoaffective disorder (PANSS total, –3.2; CDSS total, –0.5) or a mood disorder (MADRS total, 0.3; YMRS total, –1.0). Over one-third of study participants had a lifetime history of suicidal ideation or behavior (KINECT 3/4, 41%; rollover, 38%). Most participants had no C-SSRS suicidal ideation at study baseline; of these, >90% had no emergence of suicidal ideation at any time during the study (KINECT 3/4, 93% [276/296]; rollover, 98% [153/156]).
Valbenazine was well tolerated and no unexpected safety signals were found in adults who received >1 year of once-daily treatment. Psychiatric stability was maintained, and few participants experienced any emergence of suicidal ideation during the studies despite 35–40% having a lifetime history of suicidality. These results indicate that once-daily valbenazine may be an appropriate treatment for the long-term management of TD.
Funding Acknowledgements: Neurocrine Biosciences, Inc.
Valbenazine (VBZ) is a novel vesicular monoamine transporter 2 (VMAT2) inhibitor approved to treat tardive dyskinesia (TD) in adults. It has been evaluated in 2 long-term studies (KINECT 3, KINECT 4) in which participants received VBZ (40 or 80mg) for up to 48weeks. This long-term rollover study (NCT02736955) was conducted to evaluate global TD improvement and patient satisfaction with once-daily VBZ.
Key eligibility criteria: age 18 to 85 years; completion of KINECT 3 or KINECT 4; maintenance medications (for schizophrenia, schizoaffective disorder, or mood disorder) at stable doses; Brief Psychiatric Rating Scale score <50; no significant risk of active suicidal ideation or behavior. Following washout of prior VBZ treatment (Weeks 48 to 52 of KINECT 3 and KINECT 4), participants were re-initiated at 40mg (4weeks) and escalated to 80mg based on tolerability and clinical assessment of TD; dose was reduced to 40mg if 80mg was not tolerated (80/40mg). If unable to tolerate the 40mg dose, the participant was discontinued. Participants received open-label VBZ for up to 72weeks or until commercial availability. Assessments included Clinical Global Impression of Severity-TD (CGIS-TD: range, 1[“normal, not at all ill”] to 7[“among the most extremely ill patient”]) and Patient Satisfaction Questionnaire (PSQ: range, 1[“very satisfied”] to 5[“very dissatisfied”]).
160 participants with available data were included in analyses (40mg =35; 80mg =117; 80/40mg =8); 138 were receiving treatment when VBZ became commercially available. The percentages of participants who completed visits at Wks 12, 24, 36, and 48 were 96.3%, 78.1%, 56.9% and 35.0%, respectively. Few reached Wk 60 (n=4) or Wk 72 (n=0) due to commercial availability. The percentage of participants with CGIS-TD score ≤2 (“normal, not at all ill” or “borderline ill”) increased from baseline (before restarting VBZ) (40mg, 5.7%; 80mg, 18.1%) to Wk 48 (40mg , 41.7%; 80mg , 74.4%). At baseline, almost all participants rated their prior VBZ experience with a PSQ score ≤2 (“very satisfied” or “somewhat satisfied”) (40mg , 100%, 80mg , 99.1%). Similar results were seen at the Wk 48 visit, with most participants continuing to express satisfaction with VBZ (40mg , 100%; 80mg , 97.4%).
A clinician-based global assessment indicated ongoing, meaningful TD improvements in adults who received once-daily VBZ in the current study. In participants treated for >1 year, continued patient satisfaction rates with VBZ were high.
Funding Acknowledgements: Neurocrine Biosciences, Inc.
Herbicide resistance is ‘wicked’ in nature; therefore, results of the many educational efforts to encourage diversification of weed control practices in the United States have been mixed. It is clear that we do not sufficiently understand the totality of the grassroots obstacles, concerns, challenges, and specific solutions needed for varied crop production systems. Weed management issues and solutions vary with such variables as management styles, regions, cropping systems, and available or affordable technologies. Therefore, to help the weed science community better understand the needs and ideas of those directly dealing with herbicide resistance, seven half-day regional listening sessions were held across the United States between December 2016 and April 2017 with groups of diverse stakeholders on the issues and potential solutions for herbicide resistance management. The major goals of the sessions were to gain an understanding of stakeholders and their goals and concerns related to herbicide resistance management, to become familiar with regional differences, and to identify decision maker needs to address herbicide resistance. The messages shared by listening-session participants could be summarized by six themes: we need new herbicides; there is no need for more regulation; there is a need for more education, especially for others who were not present; diversity is hard; the agricultural economy makes it difficult to make changes; and we are aware of herbicide resistance but are managing it. The authors concluded that more work is needed to bring a community-wide, interdisciplinary approach to understanding the complexity of managing weeds within the context of the whole farm operation and for communicating the need to address herbicide resistance.
Seven half-day regional listening sessions were held between December 2016 and April 2017 with groups of diverse stakeholders on the issues and potential solutions for herbicide-resistance management. The objective of the listening sessions was to connect with stakeholders and hear their challenges and recommendations for addressing herbicide resistance. The coordinating team hired Strategic Conservation Solutions, LLC, to facilitate all the sessions. They and the coordinating team used in-person meetings, teleconferences, and email to communicate and coordinate the activities leading up to each regional listening session. The agenda was the same across all sessions and included small-group discussions followed by reporting to the full group for discussion. The planning process was the same across all the sessions, although the selection of venue, time of day, and stakeholder participants differed to accommodate the differences among regions. The listening-session format required a great deal of work and flexibility on the part of the coordinating team and regional coordinators. Overall, the participant evaluations from the sessions were positive, with participants expressing appreciation that they were asked for their thoughts on the subject of herbicide resistance. This paper details the methods and processes used to conduct these regional listening sessions and provides an assessment of the strengths and limitations of those processes.
Habitat fragmentation creates habitat edges, and ecological edge effects can cause major changes in the ecology and distribution of many taxa. However, these ecological changes may in turn influence animal movements and lead to molecular edge effects and edge-related genetic structure, matters that are largely unexplored. This study aims to infer molecular edge effects and to test three possible underlying mechanisms in the Endangered golden-brown mouse lemur Microcebus ravelobensis, a nocturnal species in the dry deciduous forest of the Ankarafantsika National Park in north-western Madagascar. Mouse lemurs were sampled in one edge and two interior habitats in close proximity to each other (500–1,400 m) in a continuous forest. A total of 41 mouse lemur samples were genotyped with seven nuclear microsatellites, and a fragment of the mitochondrial control region was sequenced for all samples. The overall genetic diversity (allelic richness, heterozygosity, haplotype richness, nucleotide diversity) was lower in the edge habitat compared to the two interior sites and all subpopulations showed signals of relatively low genetic exchange and significant genetic differentiation between them despite the short geographical distances, supporting the local preference model. These findings can be interpreted as preliminary signals of a molecular edge effect and suggest the potential for local adaptation. They are highly relevant for the conservation of fragmented populations, because a further subdivision of already small populations may increase their vulnerability to stochastic demographic changes and collapse.
Gravitational interactions allow one to investigate the nature of matter in the universe independent of the properties that make it luminous. Much as studies of the dynamics of galaxies and clusters of galaxies have indicated the presence of dark matter, gravitational lensing provides an independent probe of the large scale distribution of dark matter in the universe.
Preston et al (1976) and Burke (1982, these proceedings) have long extolled the virtues of launching a radio telescope into space to increase VLBI baseline lengths and thus angular resolution, and to provide a much enhanced image formation capability. The scientific motivation for this has been covered in a number of memoranda referenced by Burke in these proceedings, and by Anderson et al (1982). Efforts to mobilise western astronomical support for space VLBI met with success in late 1982 at a meeting of US and European radio astronomers in Toulouse, France, at which a decision was taken to propose a joint mission to ESA and NASA. Shortly thereafter, a formal proposal was made to ESA (Anderson et al 1982) for a free flying satellite in an elliptical orbit out to 15000 km from the Earth, designed to observe in concert with the major ground-based VLBI networks and arrays. The mission, dubbed QUASAT, was received favourably in both ESA and NASA, with the result that formal Assessment Studies are scheduled to begin in both agencies in October 1983.
A proposal has been made to use the Tracking and Data Relay Satellite System (TDRSS) as an orbiting element for a very long baseline interferometry (VLBI) demonstration. The TDRSS is a satellite system designed to coherently track and relay data between other satellites and the central ground station. This system could also be used to coherently observe a celestial radio source. A ground-based frequency standard would be used to coherently drive the spacecraft receiver local oscillator and transmitter. The data will be telemetered to a ground station, where it will be recorded on a Mark III terminal.
On June 1, 1984 we conducted a seven station 18-cm VLBI observation of the 2016+112 gravitational lens system. Preliminary brightness distributions for A and B have been obtained via model fitting. Weak correlated flux density was detected in the C component region.
An antenna in geostationary orbit was used for VLBI observations at 2.3 GHz, in combination with ground antennas in Australia and Japan. 23 of the 25 observed sources were detected on orbiter-ground baselines, with baseline lengths as large as 2.15 earth diameters. Brightness temperatures between 1012 K and 4 × 1012 K were measured for 10 sources.
The Dark Energy Survey is undertaking an observational programme imaging 1/4 of the southern hemisphere sky with unprecedented photometric accuracy. In the process of observing millions of faint stars and galaxies to constrain the parameters of the dark energy equation of state, the Dark Energy Survey will obtain pre-discovery images of the regions surrounding an estimated 100 gamma-ray bursts over 5 yr. Once gamma-ray bursts are detected by, e.g., the Swift satellite, the DES data will be extremely useful for follow-up observations by the transient astronomy community. We describe a recently-commissioned suite of software that listens continuously for automated notices of gamma-ray burst activity, collates information from archival DES data, and disseminates relevant data products back to the community in near-real-time. Of particular importance are the opportunities that non-public DES data provide for relative photometry of the optical counterparts of gamma-ray bursts, as well as for identifying key characteristics (e.g., photometric redshifts) of potential gamma-ray burst host galaxies. We provide the functional details of the DESAlert software, and its data products, and we show sample results from the application of DESAlert to numerous previously detected gamma-ray bursts, including the possible identification of several heretofore unknown gamma-ray burst hosts.
A lack of information regarding weed control, relative to conventional
systems, has left organic growers largely on their own when devising weed
management systems for organic crops. As interest in organic weed management
increases, researchers need more information regarding the type and number
of weed control practices undertaken on organic farms. A survey of certified
organic growers was conducted in five states in the northwest United States
to identify organic weed management programs and what grower and
farm-operation characteristics were factors in weed management program
design. Three types of weed management programs, with varying diversity in
weed control practices, were identified. Stepwise binary logistic regression
indicated that the likelihood of an organic grower using a more-diverse weed
management program increased if the grower engaged in grain production and
as the number of crops produced on an organic farm operation in 1 yr
increased. The probability of operating a more-diverse weed management
program also increased as a grower's education level increased. Organic
hectarage operated was positively correlated with weed management program
diversity, and with the adoption of cultural controls. Additionally,
awareness of weeds as a factor causing yield loss was correlated with
increased weed management program diversity. An increased awareness among
researchers of the differing needs and abilities of organic growers in
managing weeds on their farms will improve communication and outreach
efforts when assisting growers with designing organic weed management
Gravitational lens surveys are of cosmological interest because they provide a way to measure the gravitational field of both luminous and dark matter. Many of the other methods used to detect the presence of dark matter, such as studies of galaxy rotation curves and cluster dynamics, require that there be luminous objects in the gravitational field that act as tracers of the mass. This may introduce a selection effect. In constrast, in studies of gravitational lenses, the beacon we observe can be far (at distances of order one thousand Mpc) from the gravitational field. In this paper we describe a VLA survey designed to detect gravitational lensing on sub-arc second and arc second scales. We also present a preliminary result of the radio data: we find that the density of matter in the form of a uniform, comoving number density of 1011 to 1012M⊙ compact objects, luminous or dark, must be substantially less than the critical density.